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Role of TET enzymes in DNA methylation, development, and cancer
Open accessAbstract
The pattern of DNA methylation at cytosine bases in the genome is tightly linked to gene expression, and DNA methylation abnormalities are often observed in diseases. The ten eleven translocation (TET) enzymes oxidize 5-methylcytosines (5mCs) and promote locus-specific reversal of DNA methylation. TET genes, and especially TET2 , are frequently mutated in various cancers, but how the TET proteins contribute to prevent the onset and maintenance of these malignancies is largely unknown. Here, we highlight recent advances in understanding the physiological function of the TET proteins and their role in regulating DNA methylation and transcription. In addition, we discuss some of the key outstanding questions in the field.
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“Generally, 2OGO catalyze specific hydroxylation of substrates, which, in turn, leads to demethylations via other catalytic cycles or downstream pathway involving thymine-DNA-glycosylase, which catalyzed base excision with DNA base excision repair [101,120].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [120]
Experimental — accuracy not yet measuredIn the citing paper
“TET2 is frequently mutated or lost somatically in both myeloid and lymphoid malignancies63,64.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [63]
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“Thus, it was remarkable when ten eleven translocation protein 1 (TET1) was discovered and shown to be able to modify methylcytosine and potentially erase DNAmethylation (Tahiliani et al. 2009).”
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“Second, TET2 mutations are frequently observed in aged healthy individuals with clonal hematopoiesis and increase the propensity to develop hematopoieticmalignancies (Busque et al. 2012; Genovese et al. 2014; Jaiswal et al. 2014; Xie et al. 2014).”
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“Subsequent to the discovery of oxidized 5mC bases, it was demonstrated that TDG has no effect on 5hmC but shows robust recruitment and in vitro catalytic activity toward 5fC and 5caC (He et al. 2011; Maiti and Drohat 2011; Spruijt et al. 2013).”
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“By comparison, the products of further TET-mediated oxidation, 5fC and 5caC, are observed at ∼10-fold to 100-fold lower levels than 5hmC and often close to or under the detection limit (Kriaucionis and Heintz 2009; Globisch et al. 2010; Szwagierczak et al. 2010; He et al. 2011; Ito et al. 2011; Pfaffeneder et al. 2011…”
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Coira, I. F., Rincón, R., & Cuendet, M. (2022) · Cancers · doi:10.3390/cancers14102348 · Cited by 16
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“DNA methylation—a major molecular mechanism of epigenetic changes—has been recognized as an important event in many cancer types, including lung cancer.([9,10]) Studies have shown that gene methylation in the promoter regions regulates the silencing of tumor suppressor genes (TSGs), leading to the down-regulation of g…”
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“Increasing evidence suggested that 5‐hmC, which is regulated by TET2, plays an important role in various diseases, such as immune system disorders, hematopoietic diseases and cancers (5,6,8).”
Belrose, J. L., Prasad, A., Sammons, M. A., Gibbs, K. M., & Szaro, B. G. (2020) · BMC Genomics · doi:10.1186/s12864-020-06954-8 · Cited by 15
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“DNMT is responsible for maintaining DNA methylation through cellular division, and the TET family of enzymes mediate active demethylation [46,47].”
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Wan, F., Tang, Y., Tang, X.-L., Li, Y., & Yang, R. (2021) · PubMed Central · Cited by 15
Zhao, H., Fu, W., Yang, X., Zhang, W., Wu, S., Ma, J., Zhang, T., Yao, H., & Zhang, Z. (2025) · Genes & Diseases · doi:10.1016/j.gendis.2025.101742 · Cited by 15
“50 Studies have shown that vitamin C enhances TET enzyme activity, promoting DNA demethylation and reversing tumor-associated DNA hypermethylation patterns.”
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“These results may imply that distal regulatory regions with enhancer features are dependent on TET2-mediated DNA demethylation and may correlate with the presence of additional mechanisms that control DNA methylation status at promoter-associated regions (62,63).”
BackgroundDeciphering adipose development: Function, differentiation and regulation
Guo, G., Wang, W., Tu, M., Zhao, B., Han, J., Li, J., Pan, Y., Zhou, J., Ma, W., Liu, Y., et al. (2024) · Developmental Dynamics · doi:10.1002/dvdy.708 · Cited by 16
“308 Tet family members that oxidize 5mC to 5-hydroxymethylcytosine (5hmC) including TET1, TET2 and TET3, which are involved in DNA demethylation 309 (Table 4).”
DNA methylation modification in Idiopathic pulmonary fibrosis
Ren, L., Chang, Y., Jiang, S.-H., Li, X.-H., & Cheng, H. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1416325 · Cited by 14
“All TET proteins contain a conserved double-stranded β -helical domain, a cysteine-rich domain, cofactor Fe ( Ⅱ ), and 2-oxoglutarate (Rasmussen and Helin, 2016).”
BackgroundWang, X., Wang, Y., Xie, M., Ma, S., Zhang, Y., Wang, L., Ge, Y., Li, G., Zhao, M., Chen, S., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07109-3 · Cited by 14
“TET1 is a tumor suppressor that is required for DNA demethylation, which counters the effects of DNA methyltransferase-induced CGI hypermethylation and gene expression suppression [38].”
DNA Methylation in Prostate Cancer: Clinical Implications and Potential Applications
Muletier, R., Bourgne, C., Guy, L., & Dougé, A. (2025) · Cancer Medicine · doi:10.1002/cam4.70528 · Cited by 14
“They are less common in solid tumors, with a frequency of up to 10% in some studies [26].”
A disease-modifying treatment for Alzheimer’s disease: focus on the trans-sulfuration pathway
Berry, T. M., Hamza, E. A., & Moustafa, A. A. (2019) · Reviews in the Neurosciences · doi:10.1515/revneuro-2019-0076 · Cited by 14
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“Due to the importance of methylation marks in the control of developmental gene expression, addition and removal of a methyl group to the 5-position of cytosine (5mC) is tightly controlled by DNA methyltransferases (DNMTs) and teneleven translocation (TET) methylcytosine dioxygenases, respectively (Li and Zhang, 2014;…”
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Bhandari, Y. R., Krishna, V., Powers, R., Parmar, S., Thursby, S.-J., Gupta, E., Kulak, O., Gokare, P. R., Reumers, J., Wesenbeeck, L. V., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2301536120 · Cited by 15
“As 5 hmC and 5 mC can have differential roles in gene regulation (73), future studies should analyze alterations in TF activities in relation to 5 mC and 5 hmC alterations.”
BackgroundDeciphering the Epigenetic Code in Embryonic and Dental Pulp Stem Cells.
Bayarsaihan, D. (2016) · Europe PMC (PubMed Central) · Cited by 14
Arvaniti, P., Zachou, K., Lyberopoulou, A., Gatselis, N., Brooks, W. H., Dalekos, G. N., & Renaudineau, Y. (2019) · Epigenomes · doi:10.3390/epigenomes3030015 · Cited by 14
“An active DNA demethylation process was recently described involving the TET enzyme family (TET1,2,3), which oxidizes 5mC into 5-hydroxymethylcytosine (5hmC) and, subsequently, in a less efficient fashion, into 5-formylcytosine (5-fCyt) and 5-carboxylcytosine (5-CaCyt) with the use of α-ketoglutarate (α-KG), molecular…”
BackgroundChen, S., Zhou, Q., Liu, T., Zhang, W., Zeng, X., & Guo, Z. (2019) · Journal of Cancer · doi:10.7150/jca.38283 · Cited by 14
“Several important studies showed DNA methyltransferases could catalyze and maintain the transformation of cytosine to methyl cytosine, but the Ten-Eleven-Translocation (TET) family of TET1, TET2 and TET3 mediate the reverse process [17-19].”
BackgroundZahoor, A., Khazer, R., Mehraj, I., Gani, U., Fayaz, F., Khanday, F. A., & Saleem, S. (2025) · Functional & Integrative Genomics · doi:10.1007/s10142-025-01552-x · Cited by 13
“Caveolin-1 silencing increases autophagy via p53-dependent cell cycle arrest (Ha et al. 2012; Rasmussen and Helin 2016).”
Wang, X., Sarver, A. L., Han, Q., Seiler, C. L., Xie, C., Lu, H., Forster, C. L., Tretyakova, N. Y., & Hallstrom, T. C. (2022) · Development · doi:10.1242/dev.195644 · Cited by 14
Advances in the understanding and treatment of Cutaneous T-cell Lymphoma
Bakr, F. S., & Whittaker, S. J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1043254 · Cited by 13
“A second type of DNA methylation involves 5-hydroxymethylation of cytosine which is mediated by ten-eleven translocation 1-3 enzymes (TET1-3) but, in contrast to 5-methylcytosine, this is associated with enhanced gene expression (38).”
BackgroundHu, L., Hu, J., Huang, Y., Zheng, S., Ji, Y., Li, X., Li, D., Lv, C., Li, S., & Hu, W. (2023) · Medicine · doi:10.1097/md.0000000000032533 · Cited by 18
“When the PI3K/AKT/mTOR signaling cascade is active, HIF1α protein translation and mRNA transcription are both increased.[54] Multiple growth factors, oncogene activation, and tumor suppressor gene alterations (such as PTEN) could all stimulate HIF1α signaling via the PI3K/AKT/mTOR pathway.”
BackgroundInfluentialDevelopment of Novel Epigenetic Anti-Cancer Therapy Targeting TET Proteins
Kim, H., Jung, I., Lee, C. H., An, J., & Ko, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216375 · Cited by 14
“In particular, TET2 LOF mutations are recurrent in patients with myeloid and lymphoid malignancies, and mice with the targeted inactivation of their TET proteins in hematopoietic cells succumbed to diverse types of hematological malignancies [3,8,10,11].”
BackgroundBridging tissue repair and epithelial carcinogenesis: epigenetic memory and field cancerization
Levron, C. L., Elettrico, L., Duval, C., Piacenti, G., Proserpio, V., & Donati, G. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-023-01254-6 · Cited by 15
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Epigenetic Regulation in Myocardial Fibroblasts and Its Impact on Cardiovascular Diseases
Komal, S., Gao, Y., Wang, Z., Yu, Q., Wang, P., Zhang, L., & Han, S. (2024) · Pharmaceuticals · doi:10.3390/ph17101353 · Cited by 14
“They catalyze the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), respectively, as part of the process of DNA demethylation [41,42].”
BackgroundSkin Rejuvenation by Modulation of DNA Methylation
Grönniger, E., Max, H., & Lyko, F. (2024) · Experimental Dermatology · doi:10.1111/exd.70005 · Cited by 13
“DNMT activity is antagonised by the TET dioxygenases, that catalyse the oxidation of 5-methylcytosine, resulting in DNA demethylation [4].”
Altered DNA methylation and miRNA expression: epi-marks for elucidating the pathophysiology of PCOS
Bhingardeve, S., Sagvekar, P., & Mukherjee, S. (2025) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2025.104838 · Cited by 14
Analog epigenetic memory revealed by targeted chromatin editing
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“12,45,69 This enzyme then modulates the constants k ′ T and k ′∗ T in the reactions of Table S5.”
Riso, G. D., Fiorillo, D. F. G., Fierro, A., Cuomo, M., Chiariotti, L., Miele, G., & Cocozza, S. (2020) · Biomolecules · doi:10.3390/biom10091271 · Cited by 12
“The latter can both reflect the refractoriness of low methylated regions to be methylated, or be the result of the preferential binding of TETs to unmethylated CpGs, and of their processivity [4,18].”
BackgroundBonora, M., Kahsay, A., & Pinton, P. (2021) · International review of cytology · doi:10.1016/bs.ircmb.2021.05.003 · Cited by 16
Reverdatto, S., Prasad, A., Belrose, J. L., Zhang, X., Sammons, M. A., Gibbs, K. M., & Szaro, B. G. (2022) · BMC Genomics · doi:10.1186/s12864-021-08247-0 · Cited by 13
“IDH1 metabolically upregulates TET enzymatic activity, promoting conversion of 5mC to 5hmC [94, 118], and PRMT1 associates with hydroxymethylated sites along DNA, where it methylates histones to regulate transcription [107].”
BackgroundEpigenetic aberrations of gene expression in a rat model of hepatocellular carcinoma
Boycott, C., Beetch, M., Yang, T., Lubecka, K., Ma, Y., Zhang, J., Kurzava, L., Ullmer, M., Ramsey, B. S., Torregrosa‐Allen, S. E., et al. (2022) · Epigenetics · doi:10.1080/15592294.2022.2069386 · Cited by 13
“, Ten-Eleven Translocation, TET proteins) [19,20].”
CpG Islands: A Historical Perspective
Antequera, F., & Bird, A. P. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7768-0_1 · Cited by 14
“In addition, unscheduled methylation of CGIs could be actively removed by the TET proteins, which are also members of the CxxC protein family [76].”
BackgroundLai, Y., Audira, G., Liang, S., Siregar, P., Suryanto, M. E., Lin, H., Villalobos, O. A., Villaflores, O. B., Hao, E., Lim, K., et al. (2020) · Genes · doi:10.3390/genes11111322 · Cited by 13
“The add on and off of methyl group onto DNA without altering protein-coding sequences is catalyzed by DNA methyltransferases (DNMTs) and demethylase (TETs) [2,3].”
BackgroundAnalog epigenetic memory revealed by targeted chromatin editing
Palacios, S., Bruno, S., Weiss, R., Salibi, E., Kane, A., Ilia, K., & Del Vecchio, D. (2024) · doi:10.1101/2024.02.13.580200 · Cited by 13
HOXA10 and HOXA11 Methylation: Epigenetic Barriers to Endometrial Receptivity in ART
Kudlay, D. A., Kiselev, V. I., & Sukhikh, G. T. (2025) · Genes · doi:10.3390/genes16101230 · Cited by 12
“For a long time, DNA methylation was considered a stable epigenetic event that suppresses gene expression and is faithfully transmitted to daughter cells only during DNA replication [71].”
TET1 Isoforms Have Distinct Expression Pattern, Localization and Regulation in Breast Cancer
Alzahayqa, M., Jamous, A., Khatib, A., & Salah, Z. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.848544 · Cited by 12
“TET enzymes have common as well as distinct functions in embryonic development, stem cell biology, cell differentiation as well as neuronal cell biology (8).”
BackgroundLiang, X., Arányi, T., Zhou, J., Guan, Y., Hu, H., Liu, H., & Suszták, K. (2022) · Journal of the American Society of Nephrology · doi:10.1681/asn.2022040460 · Cited by 12
Belle, R., Saraç, H., Salah, E., Bhushan, B., Szykowska, A., Roper, G., Tumber, A., Kriaučionis, S., Burgess-Brown, N., Schofield, C. J., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01820 · Cited by 13
Shi, F., Li, S., Zhou, M., Lv, C., Li, Y., Luo, C., Liu, N., Lu, J., Tang, M., Luo, X., et al. (2024) · Journal of Medical Virology · doi:10.1002/jmv.29634 · Cited by 12
“21 As the most abundant and stably oxi ‐ mC, 5hmC becomes a demethylation ‐ independent marker.”
BackgroundExploring the pathogenesis of pulmonary vascular disease
EJIKEME, C. P., & Safdar, Z. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1402639 · Cited by 12
“These oxidized forms of cytosine enable DNA methylation through both active and passive mechanisms (87–89).”
BackgroundLiang, X., Liu, H., Hu, H., Ha, E., Zhou, J., Abedini, A., Sánchez‐Navarro, A., Klötzer, K. A., & Suszták, K. (2024) · Nature Communications · doi:10.1038/s41467-024-53798-x · Cited by 12
“TET2 is widely expressed in the body 48 .”
Epigenetic Control of Redox Pathways in Cancer Progression
Shah, V., Lam, H. Y., Leong, C. H.-M., Sakaizawa, R., Shah, J., & Kumar, A. P. (2025) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0465 · Cited by 12
“Particularly, 5mC is oxidized stepwise into 5hmC (5-hydroxymethylcytosine), 5fC (5-for-mylcytosine), and 5caC (5-carboxycytosine) followed by base excision repair (Rasmussen and Helin, 2016).”
Kang, D. H., Jeong, D. J., Ahn, T. S., Lee, H. Y., Kim, H. J., Bae, S. B., Kim, H. J., Lee, M. S., Kwon, H. Y., & Baek, M. J. (2021) · Oncology Letters · doi:10.3892/ol.2021.12425 · Cited by 12
“DNA methylation occurs throughout the genome and is constantly maintained during the replication process (36).”
BackgroundEpigenetic modifications of the renin–angiotensin system in cardiometabolic diseases
Elgazzaz, M., & Lazartigues, E. D. (2021) · Clinical Science · doi:10.1042/cs20201287 · Cited by 13
Fong, J., Gardner, J. R., Andrews, J. M., Cashen, A. F., Payton, J. E., Weinberger, K. Q., & Edwards, J. R. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab516 · Cited by 11
“An additional consideration is that DXM does not consider 5-hydroxymethylation (5hmC), which may impact interpreting results in samples with high levels of 5hmC, such as neuronal cell types (59).”
BackgroundRivas, M. A., Durmaz, C., Kloetgen, A., Chin, C. R., Chen, Z., Bhinder, B., Koren, A., Viny, A. D., Scharer, C. D., Boss, J. M., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.688493 · Cited by 12
“Tet2 normally mediates enhancer cytosine hydroxymethylation whereas Kmt2d mediates enhancer H3K4 mono and demethylation (60, 61).”
BackgroundLiu, N.-T., Perng, C., Chou, Y., Ko, P.-S., Lin, Y., Lin, Y., Chang, C., Wang, Y., Shang, H., & Chao, T. (2021) · PLoS ONE · doi:10.1371/journal.pone.0259330 · Cited by 12
The epigenetic regulation of the germinal center response
Wu, S., Yin, Y., & Wang, X. (2022) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2022.194828 · Cited by 12
Exploring links between 2‐oxoglutarate‐dependent oxygenases and Alzheimer's disease
Liu, H., Xie, Y., Wang, X., Abboud, M. I., Ma, C., Ge, W., & Schofield, C. J. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12733 · Cited by 14
Willemsen, M., & Schouten, H. C. (2017) · Biomarker Research · doi:10.1186/s40364-017-0085-8 · Cited by 12
“by TET2, especially 5-hydroxymethylcytosine resulting in DNA hydroxymethylation, are stable epigenetic marks [18].”
BackgroundSedaghat, F., Cheraghpour, M., Hosseini, S. A., Pourvali, K., Teimoori‐Toolabi, L., Mehrtash, A., Talaei, R., & Zand, H. (2018) · British Journal Of Nutrition · doi:10.1017/s000711451800212x · Cited by 12
“TET methylcytosine dioxygenases are the main part of active DNA demethylation mechanism (29) .”
ME-Class2 reveals context dependent regulatory roles for 5-hydroxymethylcytosine
Schlosberg, C., Wu, D. Y., Gabel, H. W., & Edwards, J. R. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz001 · Cited by 13
“While Dnmt1 is responsible for copying and propagating 5mC during cell division (2), no similar mechanism has yet been discovered for 5hmC. Notably, 5hmC, 5fC and 5caC are found at their highest levels in post-mitotic cells, such as neurons, and are passively diluted during cell division (1).”
InfluentialDevelopment of an MSI-positive colon tumor with aberrant DNA methylation in a PPAP patient
Yamaguchi, K., Shimizu, E., Yamaguchi, R., Imoto, S., Komura, M., Hatakeyama, S., Noguchi, R., Takane, K., Ikenoue, T., Gohda, Y., et al. (2019) · Journal of Human Genetics · doi:10.1038/s10038-019-0611-7 · Cited by 12
TET2 missense variants in human neoplasia. A proposal of structural and functional classification
Bussaglia, E., Antón, R. I., Nomdedeu, J. F., & Fuentes‐Prior, P. (2019) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.772 · Cited by 14
“[Pastor, Aravind, & Rao, 2013; Rasmussen & Helin, 2016]).”
Lobo, J., Guimarães, R., Miranda‐Gonçalves, V., Monteiro‐Reis, S., Cantante, M., Antunes, L., Braga, I. C., Maurício, J., Looijenga, L. H. J., Jerónimo, C., et al. (2020) · Epigenomics · doi:10.2217/epi-2020-0066 · Cited by 12
Identification of Novel MeCP2 Cancer-Associated Target Genes and Post-Translational Modifications
Castro‐Piedras, I., Vartak, D., Sharma, M., Pandey, S., Casas, L., Molehin, D., Rasha, F. A., Fokar, M., Nichols, J., Almodóvar, S., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.576362 · Cited by 12
Khoury, L. Y. E., Fu, S., Hlady, R. A., Wagner, R. T., Wang, L., Eckel‐Passow, J. E., Castle, E. P., Stanton, M., Thompson, R. H., Parker, A. S., et al. (2021) · Clinical Epigenetics · doi:10.1186/s13148-020-00998-z · Cited by 14
Genetic alterations and oxidative stress in T cell lymphomas
Kumar, S., Dhamija, B., Attrish, D., Sawant, V., Sengar, M., Thorat, J., Shet, T., Jain, H., & Purwar, R. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108109 · Cited by 12
Nickel-induced alterations to chromatin structure and function
Gaspar, A. D., & Cuddapah, S. (2022) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2022.116317 · Cited by 11
Jin, M., Ji, J., Chen, X., Zhou, Y. Y., Wang, D., & Liu, A.-X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1066599 · Cited by 11
Dyer, M., Lin, Q. X. X., Shapoval, S., Thieffry, D., & Benoukraf, T. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad894 · Cited by 11
“In addition, methylated CpGs-binding TFs can induce demethylation by recruiting ten–eleven translocations (TET) enzymes, which in turn allows binding of TFs, whose binding is usually methylation-impeded ( 3 ).”
BackgroundOmics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma
Chang, Y., Chen, M., Yeh, C., & Hsiao, M. (2020) · Biomolecules · doi:10.3390/biom10101377 · Cited by 11
“including increased 5-methylcytosine (5mC) content, decreased 5-hydroxymethylcytosine (5hmC) and increased histone H3 lysine 79 (H3K79) demethylation [95].”
BackgroundYuan, D.-D., Wei, Z., Wang, Y., Cheng, F., Zeng, Y.-J., Yang, L., Zhang, S., Li, J.-B., & Tang, R. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.734873 · Cited by 7
Epigenetic Regulation of TET1-SP1 During Spermatogonia Self-Renewal and Proliferation
Liu, L., Wang, J., Wang, S., Wang, M., Chen, Y., & Zheng, L. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.843825 · Cited by 11
“The DNA hydroxymethylase TET1 is an important epitopemodifying enzyme (Ross and Bogdanovic, 2019).”
BackgroundRoux, B., Picou, F., Debeissat, C., Koubi, M., Gallay, N., Hirsch, P., Ravalet, N., Béné, M. C., Maigre, M., Hunault, M., et al. (2022) · Cancer Gene Therapy · doi:10.1038/s41417-022-00441-w · Cited by 12
Alsugair, Z., Képénékian, V., Fenouil, T., Gléhen, O., Villeneuve, L., Isaac, S., Hommell-Fontaine, J., & Benzerdjeb, N. (2022) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-022-03336-1 · Cited by 11
Soto, A. A., Ortiz, G., Contreras, S., Soto‐Rifo, R., & González, P. A. (2022) · Microorganisms · doi:10.3390/microorganisms10091754 · Cited by 11
Hayat, F., Khan, N. U., Khan, A. U., Ahmad, I., Alamri, A. M., & Iftikhar, B. (2022) · PLoS ONE · doi:10.1371/journal.pone.0276813 · Cited by 11
“RANKL rs9533156 (T > C) causes DNA hypermethylation leading to gene silencing and transcriptional inactivation, that affects the binding of transcriptional factors [22, 23].”
Is DNA methylation in the brain a mechanism of alcohol use disorder?
Jarczak, J., Miszczak, M., & Radwańska, K. (2023) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2023.957203 · Cited by 13
“Passive demethylation occurs due to the omission of methylation after replication (Rasmussen and Helin, 2016), while active demethylation requires the activity of AlkB or/and TET enzymes (Chen and Riggs, 2011; Figure 2).”
BackgroundInfluentialImran, H., An, J., Jang, K., Alam, A., Dharuman, V., Ko, M., & Lim, S. (2023) · Journal of Alloys and Compounds · doi:10.1016/j.jallcom.2023.169715 · Cited by 11
Omar, M. A., Alexiou, M. V., Rekhi, U., Lehmann, K., Bhardwaj, A., Delyea, C., Elahi, S., & Febbraio, M. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1164499 · Cited by 12
“Sequential oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxycytosine (5caC) is catalyzed by TET enzymes (77, 78).”
The history of genome editing: advances from the interface of chemistry & biology
Matsumoto, D., & Nomura, W. (2023) · Chemical Communications · doi:10.1039/d3cc00559c · Cited by 15
Specific Methyl-CpG Configurations Define Cell Identity through Gene Expression Regulation
Improda, T., Morgera, V., Vitale, M., Chiariotti, L., Passaro, F., Feola, A., Porcellini, A., Cuomo, M., & Pezone, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24129951 · Cited by 11
Friedreich's ataxia: new insights
Krasilnikova, M. M., Humphries, C. L., & Shinsky, E. M. (2023) · Emerging Topics in Life Sciences · doi:10.1042/etls20230017 · Cited by 12
Bräuer, K. E. M., Brockers, K., Moneer, J., Feuchtinger, A., Wollscheid-Lengeling, E., Lengeling, A., & Wolf, A. (2018) · BMC Evolutionary Biology · doi:10.1186/s12862-018-1215-0 · Cited by 12
TET mediated epigenetic regulation of iNKT cell lineage fate choice and function
Tsagaratou, A. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.08.020 · Cited by 10
Epigenetic regulation of the hypoxic response
Nam, H. J., & Baek, S. H. (2018) · Current Opinion in Physiology · doi:10.1016/j.cophys.2018.11.007 · Cited by 11
“pathway for active DNA demethylation [11].”
Terminal keratinocyte differentiation in vitro is associated with a stable DNA methylome
Smits, J. P. H., Dirks, R. A. M., Qu, J., Oortveld, M. A. W., Brinkman, A. B., Zeeuwen, P. L. J. M., Schalkwijk, J., Zhou, H., Marks, H., & van den Bogaard, E. H. J. (2020) · Experimental Dermatology · doi:10.1111/exd.14153 · Cited by 11
Epigenetic memory: The role of the crosstalk between histone modifications and DNA methylation
Vecchio, D. D. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.08.034 · Cited by 11
“Nevertheless, DNA methylation can be reversed to non-methylated forms by enzymes of the TET family, which modify methylated cytosines into forms not recognized by maintenance methylation enzymes [42].”
Epigenetically programmed resistance to chemo- and immuno-therapies
Walker, R. R., Rentia, Z., & Chiappinelli, K. B. (2023) · Advances in cancer research · doi:10.1016/bs.acr.2022.12.001 · Cited by 13
Jing, C., Prutsch, N., He, S., Zimmerman, M. W., Landesman, Y., & Look, A. T. (2023) · British Journal of Haematology · doi:10.1111/bjh.18667 · Cited by 11
Jago, S. S., Bahabry, R., Schreiber, A. M., Homola, J., Ngyuen, T., Meijia, F., Allendorfer, J. B., & Lubin, F. D. (2023) · Epilepsy & Behavior Reports · doi:10.1016/j.ebr.2023.100642 · Cited by 10
“DNA methylation is an enzymatic process mediated by DNA methyl-transferases (DNMTs) and the ten-eleven translocation (TET) enzymes [16].”
BackgroundThe TET-Sall4-BMP regulatory axis controls craniofacial cartilage development
Wang, W., Yang, N., Wang, L., Zhu, Y., Chu, X., Xu, W., Li, Y., Xu, Y., Gao, L., Zhang, B., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113873 · Cited by 10
Imran, H., Lee, H., Alam, A., An, J., Ko, M., & Lim, S. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101123 · Cited by 10
Metadata
- Authors
- Rasmussen, K. D., & Helin, K.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Helin, Kristian
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2016-04-01
- Volume
- 30
- Issue
- 7
- Pages
- 733-750
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC4826392
- OpenAlex
- W2325267338
- Cited by
- 1,040
- References
- 162
- Citations by year
- 2026: 56 · 2025: 87 · 2024: 116 · 2023: 100 · 2022: 135 · 2021: 141 · 2020: 131 · 2019: 97 · 2018: 83 · 2017: 60 · 2016: 30
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Genes & Development (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Danish Medical Research Council (1333-00120B)
- European Research Council (294666_DNAMET)
- Danish Cancer Society
- Danish National Research Foundation (DNRF 82)
- Danish Council for Strategic Research
- Novo Nordisk Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- TET enzymes, DNA methylation, 5-methylcytosine oxidation, TET2, demethylation, cancer, developmental regulation, transcriptional regulation, gene expression
- MeSH terms
- Animals, Cytosine, DNA-Binding Proteins, Humans, Neoplasms, Oxidation-Reduction, Proto-Oncogene Proteins, Gene Expression Regulation, Neoplastic, DNA Methylation, Epigenesis, Genetic, Dioxygenases
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